4-47426318-CT-CTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000812.4(GABRB1):c.*304dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 213,426 control chromosomes in the GnomAD database, including 279 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.052 (214 hom., cov: 29)
  • Exomes 𝑓: 0.038 (65 hom.)
• Consequence: GABRB1 NM_000812.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.139

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRB1	NM_000812.4	c.*304dup		3_prime_UTR_variant	9/9	ENST00000295454.8
GABRB1	XM_017007985.2	c.*304dup		3_prime_UTR_variant	5/5
GABRB1	XM_024453976.2	c.*304dup		3_prime_UTR_variant	9/9
GABRB1	XM_024453977.2	c.*304dup		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRB1	ENST00000295454.8	c.*304dup		3_prime_UTR_variant	9/9	1	NM_000812.4	P1

Frequencies

GnomAD3 genomes AF: 0.0519 AC: 7821 AN: 150622 Hom.: 216 Cov.: 29

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.0967

Gnomad SAS AF: 0.0755

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0424

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0377 AC: 2363 AN: 62684 Hom.: 65 Cov.: 0 AF XY: 0.0384 AC XY: 1219 AN XY: 31782

Gnomad4 AFR exome AF: 0.0500

Gnomad4 AMR exome AF: 0.0207

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.0572

Gnomad4 SAS exome AF: 0.0568

Gnomad4 FIN exome AF: 0.0237

Gnomad4 NFE exome AF: 0.0348

Gnomad4 OTH exome AF: 0.0390

GnomAD4 genome AF: 0.0520 AC: 7834 AN: 150742 Hom.: 214 Cov.: 29 AF XY: 0.0508 AC XY: 3734 AN XY: 73534

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.0678

Gnomad4 EAS AF: 0.0965

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.0363

Gnomad4 NFE AF: 0.0424

Gnomad4 OTH AF: 0.0604

Alfa AF: 0.0475 Hom.: 17

Asia WGS AF: 0.106 AC: 368 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3832300; hg19: chr4-47428335;